HIV continues to spread with nearly 40 million infected individuals and over 5 million newly infected every year. The principle means of infection remains heterosexual transmission. In many areas of the world, particularly Sub-Saharan Africa, HIV infection has become more prevalent in women than men (www.unaids.org). This trend in conjunction with discriminatory sexual rights for women in many parts of Asia and Africa makes it important to identify the mechanisms of male-to-female spread of HIV and to implement new methods for preventing sexual transmission. Normally, the mucosal barrier acts as a significant blockade for pathogens seeking to gain entry into the human body. HIV enters either through breaks in this barrier or through some active mechanism that allows it to transverse the mucosal barrier. Identification of mediators of transmission is therefore very desirable.
Macaque studies indicate that the first targets of SIV infection during non-traumatic vaginal application are Langerhans cells (LCs), sub-epithelial dendritic cells (DCs) and CD4+ T cells of the lower genital tract. The lower genital tract barrier is composed of a columnar monolayer in the endocervix and stratified squamous epithelium in the vagina and ectocervix along with their associated mucous and glycoprotein secretions. The necessary events in transmission preceding infection of LCs, sub-epithelial DCs and CD4+ T cells remain unclear. In vitro models of female genital tissue have been designed to explore transmission, but their in vivo relevance is controversial.
Disruption of these epithelial barriers by ulcerating lesions or other local factors allowing direct access to underlying cells capable of propagating virus is a proposed mechanism for penetrating the outer mucosa. However, infection in the presence of a seemingly undamaged epithelium also occurs. Previous experiments have suggested that primary vaginal epithelial cells can sequester and transmit HIV to activated PBMCs in culture, even though the epithelial cells do not express significant levels of virus receptors6. This indicates that other factors within this subset of cells may interact directly with HIV and facilitate virus transfer to target cells